medwireNews: People who transition to zoledronate after treatment with denosumab experience significantly greater reductions in lumbar spine bone mineral density (BMD) during the first year than those who continue with denosumab, study findings indicate.
“[H]owever, BMD in the femoral neck and total hip was preserved after sequential therapy,” report Shau-Huai Fu (National Taiwan University Hospital, Taipei) and co-authors in JAMA Network Open.
Their study included 101 individuals (94.1% postmenopausal women, median age 72 years) who had received regular denosumab treatment for at least 2 years and had not previously been exposed to other antiosteoporosis medication.
Of these, 76 stopped denosumab and were given one dose of zoledronate 5 mg instead, 6 months after their last dose of denosumab, while 25 were randomly assigned to continue with denosumab 60 mg twice yearly.
After 1 year, the researchers observed a significant difference in the median percentage change in lumbar spine BMD between the two groups. Specifically, individuals given zoledronate had a median 0.68% fall in lumbar spine BMD whereas the measurement increased by a median 1.30% among those who continued denosumab.
By contrast, there were no significant differences between the zoledronate and denosumab groups in the median change in total hip BMD (0 vs 1.12%) and femoral neck BMD (0.18 vs 0.17%) at 1 year.
Fu et al note that further analyses “suggested that a longer duration of continuous denosumab treatment before sequential therapy (specifically ≥3 years) negatively affected the efficacy of zoledronate in preserving bone mass.”
Indeed, participants who switched to zoledronate after 3 or more years of denosumab treatment experienced a median 3.20% reduction in lumbar spine BMD at 1 year. Conversely, the reduction was just 0.28% for those with less than 3 years of prior denosumab treatment and was noninferior to the 1.30% increase observed among the participants given continuous denosumab treatment.
Furthermore “the results of our multivariable analysis suggest that sequential therapy with zoledronate before the third year of continuous denosumab treatment (ie, before the sixth dose of denosumab) was more likely to preserve bone mass,” the investigators remark.
They conclude: “Further randomized clinical trials and large-scale studies that investigate the strategies of sequential therapy after long-term denosumab treatment are needed.”
The authors also note that all study participants were Asian and therefore say that “further investigation is needed for generalizability of the findings.”
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